Interlocked feedback loops within the Drosophila circadian oscillator
Interlocked feedback loops within the Drosophila circadian oscillator
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DOI：
10.1126/science.286.5440.766
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发表时间：
1999-10-22
期刊：
影响因子：
56.9
通讯作者：
Hardin, PE
中科院分区：
文献类型：
--
作者：
Glossop, NRJ;Lyons, LC;Hardin, PE
果蝇时钟(DClk)是有节律性的表达，在清晨的mRNA和蛋白质(Dclk)丰度达到高峰。DClk mRNA的循环受无时间周期(PER-TIM)介导的依赖于dCLK和周期(CyC)抑制的释放所调节。缺乏Per-Tim去抑制和dCLK-CyC抑制导致高水平的dClk mRNA，这意味着存在一个单独的dClk激活子。这些结果表明，果蝇昼夜节律反馈环由两个相互连锁的负反馈环组成：一个由dCLK-CyC激活、由Per-TIM抑制的Per-TIM环和由dCLK-CyC抑制、由Per-TIM解除抑制的dClk环。
Drosophila Clock (dClk) is rhythmically expressed, with peaks in mRNA and protein (dCLK) abundance early in the morning. dClk mRNA cycling is shown here to be regulated by PERIOD-TIMELESS (PER-TIM)-mediated release of dCLK- and CYCLE (CYC)-dependent repression. Lack of both PER-TIM derepression and dCLK-CYC repression results in high levels of dClk mRNA, which implies that a separate dClk activator is present. These results demonstrate that the Drosophila circadian feedback loop is composed of two interlocked negative feedback Loops: a per-tim loop, which is activated by dCLK-CYC and repressed by PER-TIM, and a dClk Loop, which is repressed by dCLK-CYC and derepressed by PER-TIM.